DESCRIPTION: Dentin matrix protein 1 (Dmp1) is a non-collagenous phosphoprotein found in dentin. Dmp1 is synthesized by odontoblasts as well as osteoblasts and cementoblasts, suggesting a function in biomineralization. This R03 application aims to elucidate the function of Dmp1 by generating and characterizing the phenotype of Dmp1 null mice. The hypothesis to be tested is that functional Dmp1 is essential for normal dentin. Aim 1 will introduce a null allele in the Dmp1 gene using homologous recombination in embryonic stem (ES) cells. Mutant cells will then be injected into blastocysts to generate germline chimeras carrying the targeted Dmp1 gene. Aim 2 will characterize neonatal Dmp1-/- mice by comparing them to wildtype and heterozygote animals using morphologic, radiologic, histologic and molecular approaches. The establishment of Dmp1 deficient mice and their basic characterization will provide the basis of future studies addressing the functional role of Dmp1 in dentin formation.